hGH: The primary biological function of hGH includes stimulating growth, cell repair and regeneration. Once the primary growth period of adolescence concludes, the primary function of hGH in adulthood becomes that of cell regeneration and repair, helping regenerate skin, bones, heart, lungs, liver and kidneys to their optimal, youthful cell levels. As is the case with many of our other hormones or their pre-cursors, such as testosterone, oestrogen, progesterone, DHEA and melatonin, hGH levels decline with age. Therapeutically, many of these hormones can be replaced to offset some of the effects of aging such as menopausal symptoms in women or erectile dysfunction in men. The human body, like every other living entity, works on daily, or circadian, as well as monthly and annual rhythms. Daily growth hormone secretion diminishes with age with roughly half the levels at age forty that we had when we were twenty, and about one-third of those youthful levels at age sixty. In some sixty-year olds, the levels are as low as 25% of the hGH levels in a twenty-year old. Symptoms of aging include loss of muscle, increase of fat, decreased physical mobility, decreased energy levels and as a result, diminished socialization, diminished healing ability and an increased risk of cardiovascular disease and decreased life expectancy. Low hGH levels are associated with the aging process and early of disease. For example, Rosen and Bengtsson noted an increased death rate from cardiovascular disease in hGH deficient patients (Rosen, T., Bengtsson, B. A., Lancet 336 (1990): 285-2880).
Until recently human growth hormone (hereinafter alternatively referred to as hGH) was available only in expensive injectable forms, and benefits from the restoration of hGH levels available only to those with the ability to pay. Most recently substances that can trigger the release of human growth hormone from an individual's own anterior pituitary gland have become available. These are generically referred to as secretagogues. Secretagogues have the ability to restore hGH levels, potentially to the levels found in youth. See for reference the book entitled “Grow Young With hGH” by Dr. Ronald Klatz, President of the American Academy of Anti-Aging, published in 1997 by Harper Collins.
HGH-deficient adults have marked reductions in lean body mass, and within months of hGH treatment, gains in lean body mass, skin thickness and muscle mass are observed. (Cuneo R C et al. J Appl Physiol 1991; 70:695-700; Cuneo R C et al. J Appl Physiol 1991; 70:688-694; Rudman D et al. N Engl J Med 1969; 280:1434-1438).
It is well-established that intravenous (IV) administration of some amino acids results in significant hGH secretion. Intravenous infusion of 183 mg of arginine/kg body weight in females increased hGH levels >20-fold and 30 g of arginine elevated serum hGH levels 8.6 fold in males (Merimee T J et al. N Engl J Med 1969; 280:1434-1438; Alba-Roth J et al. J Clin Endocrinol Metab 1988; 67:1186-1189). Other amino acids, such as methionine, phenylalanine, lysine, histidine, and ornithine have also led to marked increases in hGH (Alba-Roth, Muller, Schopohl, & von Werder, 1988; Chromiak & Antonio, 2002; Gourmelen, M., M. Donnadieu, et al. (1972) Ann Endocrinol (Paris) 33(5): 526-528).
Given the difficulties in IV administration of amino acids for widespread use, interest in elucidating the hGH response to oral amino acid supplements prompted testing of such supplements containing mainly arginine, lysine and ornithine at varying amounts. Yet the pronounced variability in results among these studies, which differed in aspects including subject population, supplement composition, and dosage methodologies, make clear the complexities involved in the design of an effective supplement for supporting hGH levels in the general public. (Suminski R R et al. Int J Sport Nutr 1997; 7:48-60; Lambert M I et al. Int J Sport Nutr 1993; 3:298-305; Corpas E et al. J Gerontol 1993; 48:M128-M133; Isidori A et al. Curr Med Res Opin 1981; 7:475-481; Fogelholm G M et al. Int J Sport Nutr 1993; 3:290-297; Chromiak J A, Antonio J. Nutrition 2002 July; 18(7-8):657-61).
Thus determination of an effective and safe oral functional blend that stimulates hGH secretion in the general population is important to determine since athletes, entertainers and now the general public seek effective hGH support supplements and understand hGH to have rejuvenating properties.
Indeed, once partial to athletes and entertainers, the desire for effective supplements to provoke growth hormone (hGH) increases now extends to the general public. Despite proceeding literature on oral amino acids for use in stimulating hGH, evidence for an optimized oral amino acid-containing blend able to stimulate hGH in the general public including both men and women of a wide age range is not clear.
Fibromyalgia: Scientists estimate that fibromyalgia affects 5 million Americans age 18 or older. For unknown reasons, between 80 and 90 percent of those diagnosed with fibromyalgia are women; however, men and children also can be affected. Most people are diagnosed during middle age, although the symptoms often become present earlier in life.
Fibromyalgia is a common syndrome characterized by fatigue, chronic pain, and other symptoms that are exacerbated by obesity and psychosocial factors such as stress. Furthermore, many patients with fibromyalgia exhibit diminished hGH release, as indicated by reduced insulin-like growth factor 1 (IGF-1), a mediator of hGH action and a long-term indicator of hGH levels. Fibromyalgia typically makes people feel tired and causes muscle pain and “tender points.” Tender points are places on the neck, shoulders, back, hips, arms or legs that hurt when touched. People with fibromyalgia may have other symptoms, such as trouble sleeping, morning stiffness, headaches, and problems with thinking and memory, sometimes called “fibro fog.” No one knows what causes fibromyalgia. Although fibromyalgia is often considered an arthritis-related condition, it is not truly a form of arthritis (a disease of the joints) because it does not cause inflammation or damage to the joints, muscles, or other tissues. It is this characteristic that distinguishes fibromyalgia from a disease entity, instead being as a syndrome, classified by a heterogeneous symptomology profile. Indeed, fibromyalgia can cause significant pain and fatigue, and it can interfere with a person's ability to carry on daily activities.
The causes of fibromyalgia are unknown, but there are probably a number of factors involved. Many people associate the development of fibromyalgia with a physically or emotionally stressful or traumatic event, such as an automobile accident. Some connect it to repetitive injuries. Others link it to an illness. For others, fibromyalgia seems to occur spontaneously. People with rheumatoid arthritis and other autoimmune diseases are particularly likely to develop fibromyalgia. There is no cure for fibromyalgia, but some medicines (e.g., analgesics and nonsteroidal anti-inflammatory drugs), can help manage the symptoms.
In various studies, it has been found that some of the clinical features of fibromyalgia resemble the ones described in the adult growth hormone deficiency (GHD) syndrome. Furthermore, insulin-like growth factor 1 (IGF-1) levels have been observed to be frequently reduced in patients with fibromyalgia. To that end, one study assessed 24 hour spontaneous hGH secretion, hGH responses to growth hormone-releasing hormone (GHRH), and IGF-1 and IGF binding protein 3 (IGF-BP3) levels before and after 4 days treatment with human (h)GH. It was found that, in comparison with controls, patients with fibromyalgia exhibited a marked decrease in spontaneous hGH secretion. In contrast, hGH responses to GHRH were similar in controls and in patients with fibromyalgia. Finally, treatment with hGH led to an increase in plasma IGF-1 and IGF-BP3 levels in patients with fibromyalgia. Thus, patients with fibromyalgia exhibited a marked decrease in spontaneous hGH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of hGH in patients with fibromyalgia. (Leal-Cerro et al., J Clin Endocrinol Metab 1999; 84:3378-3381).
Functional deficits in hGH secretion and use of hGH administration as a complementary treatment have been suggested for fibromyalgia. One study involving 120 patients in a placebo-controlled study investigated the efficacy and safety of low-dose hGH as an add-on therapy in patients with both severe fibromyalgia and low insulin-like growth factor 1 levels. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. Patients receiving hGH treatment showed significantly improved FIQ scores compared with placebo group. In this study, addition of hGH to the standard treatment was shown to be effective in reducing pain, showing sustained action over time. (Cuatrecasa et. al., PAIN 2012; 153:1382-1389).
In view of evidence of diminished growth hormone secretion, expressed by means of low insulin-like growth factor 1 (IGF-1) serum levels, in a subset of fibromyalgia patients, the efficacy and safety of low dose hGH as an adjunct to standard therapy in the treatment of severe, prolonged and well-treated fibromyalgia patients with low IGF-1 levels was investigated in another study. Twenty-four patients were enrolled in a randomized, open-label, controlled study, where patients were randomly assigned to receive either hGH subcutaneously (titrated depending on IGF-1) added to standard therapy or standard therapy alone during one year. The number of tender points, FIQ and the EQ-5D, including a Quality of Life visual analogic scale (EQ-VAS) were assessed at different time-points. At the end of the study, the hGH group showed a 60% reduction in the mean number of tender points (pairs) compared to the control group. Similar improvements were observed in FIQ score and EQ-VAS scale. The concomitant administration of hGH and standard therapy was well tolerated, and no patients discontinued the study due to adverse events. (Cuatrecasas et. al., BMC Musculoskeletal Disorders 2007; 8:119-127).
To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, another study assessed the clinical effects of treatment with growth hormone. Fifty women with fibromyalgia and low IGF-1 levels were enrolled in a randomized, placebo-controlled, double-blind study of 9 months' duration, where they received daily subcutaneous injections of hGH or placebo. Two outcome measures, the Fibromyalgia Impact Questionnaire and the number of fibromyalgia tender points, were evaluated at 3-monthly intervals by a blinded investigator. An unblinded investigator reviewed the IGF-1 results monthly and adjusted the hGH dose to achieve an IGF-1 level of about 250 ng/mL. Daily hGH injections resulted in a prompt and sustained increase in IGF-1 levels. The treatment group showed a significant improvement over the placebo group at nine months in both the FIQ score and the tender point score. After discontinuing growth hormone, patients experienced a worsening of symptoms. This suggests that a diminished endogenous growth hormone secretion may be responsible for some of the symptoms of fibromyalgia. (Bennett et. al., Am J Med 1998; 104:227-231).
It would be desirable to provide a nutritional supplement for elevating hGH release, in particular an amino acid-containing composition that is well tolerated having the result of increasing or elevating hGH release in individuals that have fibromyalgia or in individuals suffering from fibromyalgia symptoms, including in individuals having reduced hGH secretion. Although some existing nutritional supplements claim to impact the production of natural human growth hormone, there is a need for an improved nutritional supplement that efficiently enhances the production and effect of natural human growth hormone in patients having fibromyalgia.